A trial emulation study indirectly comparing tafamidis and acoramidis in transthyretin amyloid cardiomyopathy: the ReplicATTR study

Aim

Tafamidis and acoramidis are transthyretin stabilizers approved for the treatment of transthyretin amyloid cardiomyopathy. We compared the effectiveness of acoramidis versus tafamidis regarding allcause mortality (ACM). Materials & methods: This study used a hybrid design to compare 42-month ACM with acoramidis versus tafamidis using trial emulation, calibration, and indirect treatment comparison. Two real-world cohorts of participants initiating tafamidis were identified from TriNetX (2019–2024) using observational analogues to emulate ATTR-ACT and ATTRibute-CM trial eligibility criteria and baseline characteristics. A calibration factor was derived by comparing 42-month ACM in the ATTR-ACT tafamidis arm with the ATTR-ACT emulation cohort to quantify the net effect of systematic differences between the populations. This factor was applied to the ATTRibute-CM emulation tafamidis cohort and compared with the ATTRibute-CM acoramidis arm. Using these values and corresponding variance,Monte Carlo simulation (MCS)-estimated medians and percentile-based 95% CIs were derived.